Long-Term Outcome of Photobiomodulation for Diabetic Macular Edema: A Case Report.

Background: Macular edema is the major cause of decreased vision in patients with diabetes. Antioxidative and anti-inflammatory effects of photobiomodulation (PBM) have been reported with near-infrared irradiation. Objective: In this study, the efficacy and safety of PBM with near-infrared radiation in a patient with diabetic macular edema were assessed. Methods: We present the case of a 60-year-old man with diabetic macular edema responding to 670 nm light PBM alone. Results: After PBM, his vision improved and macular edema resolved on optical coherence tomography (OCT) findings without adverse events. In 16 months follow-up, visual acuity remained stable and OCT showed no evidence of recurrence of edema. Conclusions: Six hundred seventy nanometers light PBM can be potentially considered as a therapeutic method in diabetic patients with macular edema. Also, it provides a noninvasive and nonexpensive treatment in home.

Factors affecting the response to subthreshold micropulse laser therapy used in center-involved diabetic macular edema.

The purpose of this study was to investigate the effect of the status of retinal pigment epithelium (RPE) and HbA1c levels on the efficacy of the subthreshold micropulse laser (SMPL) in the treatment of center-involving diabetic macular edema (DME). A total of 20 eyes of 20 patients (mean age 57.9 ± 9.7 years) who were diagnosed with center-involving DME and treated with SMPL for refusing intravitreal injection and 20 eyes of 20 age- and sex-matched healthy participants were enrolled. All patients were followed up in the 1st and 3rd months after SMPL. For measurement of RPE area central 1000 microns, macular EDI-OCT scans were binarized by using the public domain software ImageJ, with a semi-automated technique. There was a significant increase in BCVA values and a significant decrease in CMT values during follow-up. The area of RPE before SMPL was significantly thinner in the patient group (p: 0.004). When the areas of RPE before and 3 months after SMPL were compared, no significant change was observed (p: 0.437). When the relationship between pre-treatment area of RPE and HbA1c was examined, an inverse correlation was observed (p: 0.018). The patients were evaluated by dividing them into 2 groups as 2nd session SMPL required and not required, and the area of RPE was smaller in the group requiring 2nd session SMPL (p: 0.030). The status of central RPE may be a determining factor on the response to treatment. Additionally, HbA1c levels may have an impact on treatment efficacy.

Preclinical and clinical studies of photobiomodulation therapy for macular oedema.

AIMS/HYPOTHESIS: Diabetic macular oedema (DME) is the leading cause of visual impairment in people with diabetes. Intravitreal injections of vascular endothelial growth factor inhibitors or corticosteroids prevent loss of vision by reducing DME, but the injections must be given frequently and usually for years. Here we report laboratory and clinical studies on the safety and efficacy of 670 nm photobiomodulation (PBM) for treatment of centre-involving DME. METHODS: The therapeutic effect of PBM delivered via a light-emitting diode (LED) device was tested in transgenic mice in which induced Müller cell disruption led to photoreceptor degeneration and retinal vascular leakage. We also developed a purpose-built 670 nm retinal laser for PBM to treat DME in humans. The effect of laser-delivered PBM on improving mitochondrial function and protecting against oxidative stress was studied in cultured rat Müller cells and its safety was studied in pigmented and non-pigmented rat eyes. We then used the retinal laser to perform PBM in an open-label, dose-escalation Phase IIa clinical trial involving 21 patients with centre-involving DME. Patients received 12 sessions of PBM over 5 weeks for 90 s per treatment at a setting of 25, 100 or 200 mW/cm2 for the three sequential cohorts of 6-8 patients each. Patients were recruited from the Sydney Eye Hospital, over the age of 18 and had centre-involving DME with central macular thickness (CMT) of >300 µm with visual acuity of 75-35 Log minimum angle of resolution (logMAR) letters (Snellen visual acuity equivalent of 20/30-20/200). The objective of this trial was to assess the safety and efficacy of laser-delivered PBM at 2 and 6 months. The primary efficacy outcome was change in CMT at 2 and 6 months. RESULTS: LED-delivered PBM enhanced photoreceptor mitochondrial membrane potential, protected Müller cells and photoreceptors from damage and reduced retinal vascular leakage resulting from induced Müller cell disruption in transgenic mice. PBM delivered via the retinal laser enhanced mitochondrial function and protected against oxidative stress in cultured Müller cells. Laser-delivered PBM did not damage the retina in pigmented rat eyes at 100 mW/cm2. The completed clinical trial found a significant reduction in CMT at 2 months by 59 ± 46 µm (p = 0.03 at 200 mW/cm2) and significant reduction at all three settings at 6 months (25 mW/cm2: 53 ± 24 µm, p = 0.04; 100 mW/cm2: 129 ± 51 µm, p < 0.01; 200 mW/cm2: 114 ± 60 µm, p < 0.01). Laser-delivered PBM was well tolerated in humans at settings up to 200 mW/cm2 with no significant side effects. CONCLUSIONS/INTERPRETATION: PBM results in anatomical improvement of DME over 6 months and may represent a safe and non-invasive treatment. Further testing is warranted in randomised clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT02181400 Graphical abstract.

Aflibercept: A Review of Its Use in Diabetic Macular Oedema.

Aflibercept (Eylea(®)) is an anti-vascular endothelial growth factor agent indicated for intravitreal use in the treatment of diabetic macular oedema. In patients with diabetic macular oedema, significantly greater improvements from baseline to week 52 in visual acuity were seen with intravitreal aflibercept versus macular laser photocoagulation in the phase III VISTA-DME and VIVID-DME trials, and versus intravitreal bevacizumab or ranibizumab in those with worse visual acuity at baseline (i.e. Early Treatment Diabetic Retinopathy Study letter score of <69) in the phase III PROTOCOL-T trial. Intravitreal aflibercept was generally well tolerated in patients with diabetic macular oedema. In conclusion, intravitreal aflibercept is an important new treatment for diabetic macular oedema.

Safety of transfoveal subthreshold diode micropulse laser for fovea-involving diabetic macular edema in eyes with good visual acuity.

PURPOSE: To determine the safety of transfoveal subthreshold diode micropulse laser for fovea-involving diabetic macular edema. METHODS: The records of all patients treated with transfoveal subthreshold diode micropulse laser for fovea-involving diabetic macular edema in two retina clinics were reviewed. The eligibility included fovea-involving diabetic macular edema by spectral domain optical coherence tomography and pretreatment visual acuity of 20/40 or better. RESULTS: Thirty-nine eyes of 27 patients aged 50 years to 87 years (mean, 69 years) were included. Postoperative follow-up ranged from 3 months to 36 months (mean, 11 months). Fourteen patients were insulin dependent, and 19 had nonproliferative retinopathy. The preoperative visual acuity was 20/20 (10 eyes), 20/25 (10 eyes), 20/30 (8 eyes), and 20/40 (11 eyes). No eye had evidence of laser-induced macular damage by any imaging means postoperatively. There were no adverse treatment effects. Logarithm of the minimum angle of resolution visual acuity was improved on average of 0.03 units at 4 months to 7 months of follow-up (P = 0.0449, paired t-test) and otherwise stable. The central foveal thickness was improved at 4 months to 7 months (P = 0.05, paired t-test) and 8 months to 12 months, postoperatively (P = 0.04, mixed model accounting). Maximum macular thickness was improved at 4 months to 7 months postoperatively (P = 0.01, paired t-test and mixed model accounting). CONCLUSION: In a small retrospective series, transfoveal subthreshold diode micropulse laser was safe and effective for the treatment of fovea-involving diabetic macular edema in eyes with good preoperative visual acuity that were not the candidates for conventional photocoagulation or intravitreal injection. Further study is warranted.

Subthreshold micropulse diode laser and double frequency neodymium: YAG laser in treatment of diabetic macular edema: a prospective, randomized study using multifocal electroretinography.

OBJECTIVE: The purpose of this study was to compare the efficacy of subthreshold micropulse diode (SDM) laser with double-frequency neodymium YAG (Nd:YAG) laser in treatment of clinically significant diabetic macular edema. METHODS: Forty-six eyes of 33 patients with clinically significant macular edema (CSME) caused by diabetic retinopathy were randomized to either SDM (810?nm) laser or the conventional double-frequency Nd:YAG (532?nm) laser. Primary outcome measures were: change in the central macular thickness as measured by optical coherence tomography (OCT) and change in macular retinal sensitivity measured using multifocal electroretinography (MfERG). Secondary outcomes were: change in best corrected visual acuity (BCVA) and contrast sensitivity. RESULTS: The group was divided in half, with 23 eyes assigned to SDM laser and 23 eyes assigned to double-frequency Nd:YAG laser. Mean follow-up period was 6 months. No statistically significant difference was noted in either the primary or the secondary outcome measures between the two groups. Macular thickness decreased from the baseline measures of 298.5?49.3 and 312.9?45.8??m to 274.9?62.9 and 286.7?32.8??m in the SDM laser and Nd:YAG laser groups, respectively. On MfERG, P1 implicit wave time delay at baseline changed from 46.27?4.9 to 45.27?3.4?ms in the SDM group and from 46.55?4.9 to 45.27?4.1?ms in the Nd:YAG group. MfERG recordings of 18 of the 23 eyes treated with double-frequency Nd:YAG laser showed areas of signal void as compared to 4 eyes treated with the SDM laser. CONCLUSIONS: SDM laser photocoagulation showed an equally good effect on visual acuity, contrast sensitivity, and reduction of diabetic macular edema (DME) as compared to conventional Nd:YAG laser photocoagulation. MfERG recordings, however, suggest that SDM laser results in better preservation of electrophysiological indices.

Bevacizumab intravítreo seguido de láser focal en el edema macular diabético difuso de progresión reciente. Caso clínico / Intravitreal bevacizumab followed by focal laser for diffuse diabetic macular edema of recent progression. A clinical case

Caso clínico: Se presenta el caso de un varón de 48años de edad con edema macular diabético (EMD)difuso en su ojo derecho (OD) de reciente progresión,que es tratado con dos inyecciones intravítreasconsecutivas de bevacizumab seguido de láserfocal, mostrando buena respuesta funcional y anatómica.Discusión: El EMD difuso es de difícil manejo ycon frecuencia precisa de multiterapias para su control.Proponemos el uso de bevacizumab intravítreocomo coadyuvante para reducir el EMD difuso deprogresión reciente, y facilitar la aplicación de fotocoagulacióncon láser(AU)

Case report:We report the case of a 48-year-old manwith diffuse diabetic macular edema of recent progressiontreated with two consecutive intravitrealinjections of bevacizumab followed by focal laser therapy,with good anatomic and functional response.Discussion: Diffuse diabetic macular edema is difficultto manage and frequently requires multipletherapies. We propose the use of bevacizumab as astrategy to reduce diffuse macular edema, facilitatingthe application of laser therapy(AU)

Large-spot subthreshold infrared laser to treat diabetic macular edema.

PURPOSE: To evaluate the efficacy of a large-spot subthreshold infrared laser protocol to treat diabetic maculopathy. METHODS: In a prospective, fellow eye, controlled case series, all patients had clinically significant diabetic macular edema (DME) treated with a single application of subthreshold infrared (810 nm) laser. If bilateral disease was present, the fellow eye was treated with conventional macular laser. The study was to include 20 patients. Visual acuity and central macular thickness (CMT) measured by optical coherence tomography (OCT) were assessed in the study and fellow eyes at baseline and 6 months, and any changes were compared. RESULTS: The 11th patient developed a choroidal infarct with subsequent profound loss of vision immediately after treatment. The study was terminated prematurely at this point. For the remaining 10 patients, there was a trend toward improvement in visual acuity in the study eye compared with the fellow eye at the 6-month follow-up (median change: +1.5 letters for study eye vs -6.5 letters for fellow eye; P = 0.08). There was also significant improvement in OCT-measured CMT in the study eye (mean decrease, 117 microm) compared with deterioration in OCT-measured CMT in the fellow eye (mean increase, 24 microm; P = 0.02). CONCLUSION: This subthreshold infrared laser protocol led to improvement in OCT-measured CMT and stabilization of vision in most subjects. The current protocol is however unpredictable and should not be used in the treatment of DME without further modification.

Effects of endogenous cyclotronic ionic resonance (ICR) on macular diabetic edema: preliminary results.

The intent in this research was to verify the effects of the application of low frequency magnetic fields to cases of macular diabetic edema. We treated six patients afflicted by non-proliferating diabetic retinopathy with macular oedema. Quantitative clinical appraisals of the retinal thickness were obtained for the Optical Coherence Tomography (OCT I). None of the cases affected by non-cystoid macular oedema (non-CMO), or with a relevant ischemic component, evidenced by retinal fluorangiography, had further worsening in their clinical course during the treatment. Only one of the patients, who underwent a long treatment period with ICR demonstrated a significant reduction of the macular edema, with no need of other invasive therapeutic procedures (intravitreous injection of triamcinolone and/or laser therapy).

Modified grid argon (blue-green) laser photocoagulation for diffuse diabetic macular edema.

One hundred sixty eyes of 92 patients with diffuse diabetic maculopathy with or without cystoid macular edema were enrolled in a prospective randomized clinical trial to determine the efficacy of "modified grid" argon (blue-green) laser photocoagulation. At the 12- and 24-month follow-ups, visual acuity significantly improved in treated eyes (P = 0.00007 and P = 0.00031, respectively) compared to the observation group. In addition, at the 12- and 24-month follow-ups, visual acuity significantly worsened in observation eyes (P = 0.00007 and P = 0.0007, respectively) compared to the treatment group. The following factors did not statistically alter the visual prognosis: a history of systemic hypertension (P = 0.2921); systemic vascular disease (P = 0.5324); cystoid macular edema (P = 0.1010); and initial poor visual acuity (P = 0.3032).